“Pain” treatment in Japan is said to be at a level lower than that in Europe and the United States. The environment in Japan for basic research concerning “pain” is greatly inferior to that in Europe and the United. States. Low social or governmental understanding concerning “pain” currently does not lead to “pain” treatment.
To improve medical care for “pain” by overcoming the current situation, activities should be promoted in Japan with cooperation among doctors in clinical practice, researchers involved in basic research, people involved in the government, and the like. There are many things that remain to be done including, in addition to an actual condition survey of “pain” treatment in Japan, efforts to examine effects on the social economy and the like, elucidation of the mechanism of “pain,” development of forms of treatment, formulation of treatment guidelines, enhanced “pain” education in the field of education, and educational activity for general people and patients, for example. Also, in preparation for the aging society of the near future, establishment of medical care for “pain” is thought to be an urgent need. This will improve the quality of life of patients suffering from “pain” and reduce the burden of social cost for medical care. It will also suppress social labor productivity loss and improve the Japanese economy.
Known major analgesic agents are largely classified as narcotic analgesics or antipyretic analgesics. Narcotic analgesics mainly act on the central nervous system and have strong analgesic effects. Narcotic analgesics act on opioid receptors. Examples of such narcotic analgesics include weak opioids (e.g., codeine) having relatively weak analgesic effects and strong opioids (e.g., morphine) having strong analgesic effects, but having chemical resistance. On the other hand, aspirin, acetaminophen, ibuprofen, indomethacin, and the like are known as antipyretic analgesics, which act mainly on the peripheral nervous system, and have moderate analgesic effects. Antipyretic analgesics generally have anti-inflammatory effects and analgesic antipyretic effects via COX inhibition. Analgesic antipyretic drugs, such as acetaminophen, lacking COX inhibitory action also exist.
Meanwhile, the present inventors have conducted various cellular biochemical analyses using the true slime mold Physarum polycephalum as an experimental material. The true slime mold has been revealed to undergo morphological changes depending on changes in exterior environment and exert significant changes in the composition and metabolism of biomembrane lipids along with its proliferation and differentiation. As a result of the structural analysis of a novel lipid component isolated and identified from haploid myxoamoeba in 1992, the lipid component was confirmed to be a substance containing cyclopropane-containing hexadecanoic acid at position sn-1 of the glycerol backbone and phosphoric acids circularly ester-linked at positions sn-2 and 3 (Murakami-Murofushi, K., et al.: Jr. Biol. Chem., 267, 21512-21517 (1992)). This substance was named PHYLPA since it is an LPA analog derived from Physarum. PHYLPA suppresses the activity of DNA polymerase α of eukaryotic cells and is obtained from a lipid fraction in which the proliferation of cultured animal cells has been suppressed. PHYLPA has been confirmed to exhibit such bioactivities. PHYLPA has characteristic fatty acids. As a result of examining the bioactivities of structural analogs prepared via organic synthesis involving substitution of the fatty acid portions with other general fatty acids, physiological effects similar to those of PHYLPA were confirmed (Murakami-Murofushi, K., et al.: Biochem. Biophys. Acta, 1258, 57-60 (1995)). Accordingly, an important structure for these physiological effects is inferred to be a cyclic phosphate structure at glycerol positions sn-2 and 3. Lipids having such a structure are collectively referred to as cyclic phosphatidic acids (cPAs). Moreover, it was demonstrated that cyclic phosphatidic acids (cPAs) are bioactive lipids universally existing not only in human sera, but also in various organisms (Kobayashi, T., et al.:. Life Sci., 65, 2185-2191 (1999)).    Non-Patent Document 1: Murakarni-Murofushi, K., et al.: J. Biol. Chem., 267, 21512-21517 (1992)    Non-Patent Document 2: Murakami-Murofushi, K., et al.: Biochem. Biophys. Acta, 1258, 57-60 (1995)    Non-Patent Document 3: Kobayashi, T., et al.: Life Sci., 65, 2185-2191 (1999)